PLL is an unusual clinical and morphologic variant of CLL which, in the more common B cell version, represents malignant transformation of a B lymphocyte at an intermediate stage of development. The immunophenotype of PLL cells, characterized by heavy cell surface staining for IgM and/or IgD and loss of mouse red blood cell receptors, suggests derivation from a slightly more mature cell than the one that gives rise to typical CLL. In patients with PLL prolymphocytic invasion accounts for massive splenomegaly and white counts of well over 100,000 per mm3 with minimal lymphadenopathy. Prolymphocytes are large cells with relatively open chromatin and prominent nucleoli. Extra material on the long arm of chromosome 14 is the most common cytogenetic abnormality. The clinical course of patients with PLL is aggressive, with median survivals usually of all stages. Combination chemotherapy regimens typically reserved for those with an unfavorable prognosis for non-Hodgkin's lymphomas probably are more effective in the treatment of patients with PLL than are the less myelosuppressive oral regimens used in CLL.